Epitopes described in "Peptides derived from murine insulin are diabetogenic in both rats and mice, but the disease-inducing epitopes are different: evidence against a common environmental cross-reactivity in the pathogenicity of type 1 diabetes."

Reference
Article Authors:V L Heath; P Hutchings; D J Fowell; A Cooke; D W Mason
Article Title:Peptides derived from murine insulin are diabetogenic in both rats and mice, but the disease-inducing epitopes are different: evidence against a common environmental cross-reactivity in the pathogenicity of type 1 diabetes.
Reference Detail
Reference ID:1007556
Abstract:Two rodent models of autoimmune type 1 diabetes have been used to investigate the role of insulin as an autoantigen in this disease. In lymphopoenia-induced diabetes in the PVG.RT1u rat, neonatal tolerization with insulin B-chain peptides, but not A-chain peptides, conferred significant protection from disease. After rechallenge of adult rats, neonatally B-chain-tolerized animals showed diminished B-chain-specific T-cell proliferation, interleukin (IL)-2 production, and interferon-gamma (IFN-gamma) production, as compared with control animals. The epitope recognized by the PVG.RT1u rat was mapped to residues 1-18 of the B-chain; T-cell lines specific for this epitope were generated, and these conferred diabetes upon adoptive transfer to irradiated syngeneic recipients. In adult nonobese diabetic (NOD) mice, subcutaneous immunization with B-chain peptide 9-23 emulsified in incomplete Freund's adjuvant (IFA) was also potent at preventing onset of diabetes. In contrast to PVG.RT1u rats, NOD mice recognized an epitope within residues 10-29 of the insulin B-chain. The data implicate insulin as a target autoantigen in type 1 diabetes but do not support a role for molecular mimicry to insulin in the pathogenesis of this disease.
Affiliations:Medical Research Council Cellular Immunology Unit, Sir William Dunn School of Pathology, Oxford, UK. heath@dnax.org
Date:1999
Reference Type:Literature
PubMed ID:10535449
Journal:Diabetes
Journal Volume:48
Article Pages:2157-65
Journal ISSN:0012-1797
Article Chemical List:Epitopes;Insulin;Interleukin-2;Peptide Fragments;Interferon-gamma
Article MeSH List:Amino Acid Sequence; Animals; Diabetes Mellitus, Type 1(immunology; physiopathology; prevention & control); Epitopes(immunology; pharmacology); Immune Tolerance; Insulin(chemistry; immunology; pharmacology); Interferon-gamma(biosynthesis); Interleukin-2(biosynthesis); Mice; Mice, Inbred NOD; Molecular Sequence Data; Peptide Fragments(immunology; pharmacology); Rats; Rats, Inbred Strains; Sequence Alignment; Sequence Homology, Amino Acid; T-Lymphocytes(immunology); Thymectomy
Curation Last Updated:2014-07-16 21:29:52